Shell Disorder Analysis Suggests That Pangolins Offered a Window for a Silent Spread of an Attenuated SARS-CoV-2 Precursor among Humans

Abstract

A model to predict the relative levels of respiratory and fecal–oral transmission potentials of coronaviruses (CoVs) by measuring the percentage of protein intrinsic disorder (PID) of the M (Membrane) and N (Nucleoprotein) proteins in their outer and inner shells, respectively, was built before the MERS-CoV outbreak. With M PID = 8.6% and N PID = 50.2%, the 2003 SARS-CoV falls into group B, which consists of CoVs with intermediate levels of both fecal–oral and respiratory transmission potentials. Further validation of the model came with MERS-CoV (M PID = 9%, N PID = 44%) and SARS-CoV-2 (M PID = 5.5%, N PID = 48%) falling into the groups C and B, respectively. Group C contains CoVs with higher fecal–oral but lower respiratory transmission potentials. Unlike SARS-CoV, SARS-CoV-2 with M PID = 5.5% has one of the hardest outer shells among CoVs. Because the hard shell is able to resist the antimicrobial enzymes in body fluids, the infected person is able to shed large quantities of viral particles via saliva and mucus, which could account for the higher contagiousness of SARS-COV-2. Further searches have found that high rigidity of the outer shell is characteristic for the CoVs of burrowing animals, such as rabbits (M PID = 5.6%) and pangolins (M PID = 5–6%), which are in contact with the buried feces. A closer inspection of pangolin-CoVs from 2017 to 2019 reveals that pangolins provided a unique window of opportunity for the entry of an attenuated SARS-CoV-2 precursor into the human population in 2017 or earlier, with the subsequent slow and silent spread as a mild cold that followed by its mutations into the current more virulent form. Evidence of this lies in both the genetic proximity of the pangolin-CoVs to SARS-CoV-2 (∼90%) and differences in N disorder. A 2017 pangolin-CoV strain shows evidence of higher levels of attenuation and higher fecal–oral transmission associated with lower human infectivity via having lower N PID (44.8%). Our shell disorder model predicts this to be a SARS-CoV-2 vaccine strain, as lower inner shell disorder is associated with the lesser virulence in a variety of viruses.

Persistence of SARS-COV-2 in body fluids: a bystander or whistle blower

“…This could be a plausible cause of presence of the virus in stool of patients infected with SARS-COV-2. Moreover, it is observed that patients having gastro intestinal symptoms like diarrhoea etc might prevent the virus from staying too long in the different areas of gastrointestinal track, thereby withstanding antimicrobial enzyme and digestive juice could possibly lead to the stage of persistent shedding of the virus in stool of these patients ( 13 ). However, more research has to be made to come to a final conclusion on this point.…”

Nursing Interventions to Prevent Delirium in Critically Ill Patients in the Intensive Care Unit during the COVID19 Pandemic—Narrative Overview

“…According to researchers this is linked with the fact that the virus is protected by its robust outer shell against the activity of anti-microbial enzymes contained in the saliva and mucus [ 45 ]. Further, because SARS-CoV-2 has evolutionary links to burrowing animals that have association with buried faeces which could remain active in the environment for a long time, extra care is need when it comes to the cleaning of and caring for delirious patients [ 46 ].…”

The Role of Protein Disorder in Nuclear Transport and in Its Subversion by Viruses

“…In fact, in the manually curated Database of Protein Disorder (DisProt) [ 91 ] viral proteins constitute over 10% of the total entries across all organisms. The plasticity endowed by viral protein disorder has been correlated with virulence [ 92 , 93 , 94 , 95 , 96 ], potentially by hindering recognition by components of the immune system, but also allowing viral proteins to interact with multiple host factors, thereby maximising their function.…”